Evidence map›Paper›PMID 35611927›Full record

ArticleGlia2022

Deletion of Tgfβ signal in activated microglia prolongs hypoxia-induced retinal neovascularization enhancing Igf1 expression and retinal leukostasis.

Ayumi Usui-Ouchi, Kevin Eade, Sarah Giles, Yoichiro Ideguchi, Yasuo Ouchi, Edith Aguilar, Guoqin Wei, Kyle V Marra, Rebecca B Berlow, Martin Friedlander

Open access · hybridAbstract read
In one paragraph

Article in Glia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Ayumi Usui-OuchiDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0003-2974-0830
Kevin EadeDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
Sarah GilesThe Lowy Medical Research Institute, La Jolla, California, USA.
Yoichiro IdeguchiDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
Yasuo OuchiGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
Edith AguilarDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
Guoqin WeiDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
Kyle V MarraDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
Rebecca B BerlowDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Martin FriedlanderDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0003-4238-9651
Scripps Research Institute · USSalk Institute for Biological Studies · USThe Lowy Medical Research Institute · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
INTEGRINS AND OCULAR ANGIOGENESISR01EY011254 · NEI · SCRIPPS RESEARCH INSTITUTE, THE · PI FRIEDLANDER, MARTIN · 1996 to 2016
$11.5M
NEI NIH HHS R01 EY011254NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-β (Tgfβ) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfβ signaling in activated microglia during retinal NV. Using a tamoxifen-inducible, microglia-specific Tgfβ receptor type 2 (Tgfβr2) knockout mouse [Tgfβr2 KO (ΔMG)] we show that Tgfβ signaling in microglia actively represses leukostasis in retinal vessels. Furthermore, we show that Tgfβ signaling represses expression of the pro-angiogenic factor, Insulin-like growth factor 1 (Igf1), independent of Vegf regulation. Using the mouse model of oxygen-induced retinopathy (OIR) we show that Tgfβ signaling in activated microglia plays a role in hypoxia-induced NV where a loss in Tgfβ signaling microglia exacerbates and prolongs retinal NV in OIR. Using human iPSC-derived microglia cells in an in vitro assay, we validate the role of Transforming Growth Factor-β1 (Tgfβ1) in regulating Igf1 expression in hypoxic conditions. Finally, we show that Tgfβ signaling in microglia is essential for microglial homeostasis and that the disruption of Tgfβ signaling in microglia exacerbates retinal NV in OIR by promoting leukostasis and Igf1 expression.

Indexed as

LeukostasisRetinal DiseasesRetinal NeovascularizationAnimalsDisease Models, AnimalHypoxiaInsulin-Like Growth Factor IMiceMice, Inbred C57BLMice, KnockoutMicrogliaNeovascularization, PathologicOxygenTransforming Growth Factor betaInsulin-Like Growth Factor IOxygenTransforming Growth Factor betaa mouse model of oxygen-induced retinopathyangiogenesisdiabetic retinopathyhypoxiainsulin like growth factor 1ischemic retinopathymicroglianeovascularizationretinopathy of prematuritytransforming growth factor

Identifiers

PMID35611927
PMCPMC9540888
OpenAlexW4281487291

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.